tbuckley/cabot-search huggingface dataset:
Bhopal Tragedy's Health Effects
Authors: Pushpa S. Mehta
Journal: JAMA (1990)

SIX YEARS AGO, on December 3, 1984, a toxic gas leak at a Union Carbide pesticide plant in Bhopal, India, released methyl isocyanate (MIC) and its reaction products. The number of persons "exposed" and "injured" remains uncertain.<sup>1</sup>Official estimates from the Indian government place the dead at around 1800.<sup>2</sup>Others estimate mortality to have been between 2500 and 5000 and the number of injured to have been up to 200 000.<sup>3,4</sup> Until the Bhopal incident, neither deaths nor cases of toxic effects from MIC exposure had been recorded in<i>Index Medicus</i>.<sup>5</sup>1 We have extensively surveyed the medical literature concerning effects of MIC exposure on the victims of the disaster and laboratory studies in animals. A great deal has been learned, but many questions still remain unanswered. <h3>THE BHOPAL PLANT</h3> In 1969, the Union Carbide Corporation built a formulation plant in Bhopal, India, to mix and
Remitting Seronegative Symmetrical Synovitis With Pitting Edema
Authors: Daniel J. McCarty
Journal: JAMA (1985)

Eight elderly men and two elderly women presented with symmetrical polysynovitis of acute onset involving most of their appendicular joints and flexor digitorum tendons associated with pitting edema of the dorsum of both hands and both feet. Onset of seven of the ten cases could be pinpointed almost to the hour. Rheumatoid factors were absent from serum samples in all, and no radiologically evident erosions developed. Clinical and laboratory signs of inflammation and the edema disappeared gradually in each case. Treatment consisted of aspirin or other nonsteroidal antiinflammatory drugs. Hydroxychloroquine, 200 to 400 mg/day, was given in six and gold therapy in two cases. Painless limitation of motion of the wrists and/or fingers persisted in all, although the patients were both unaware of and unhampered by this abnormality. Six of eight cases where typing was possible were positive for HLA-B7, CW7, and DQW2 (relative risk for B7, 9.5). Three cases of this syndrome were found in a consecutive series of 52 men diagnosed as having definite "rheumatoid arthritis," and thus represent a distinctive condition with an excellent prognosis. (<i>JAMA</i>1985;254:2763-2767)
Effect of Hepatic Injury on Induction of Adrenal Necrosis and Mammary Cancer by 7,12-Dimethylbenz[&lt;italic&gt;a&lt;/italic&gt;]anthracene in rats&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Journal: JNCI Journal of the National Cancer Institute (1965)

The effects of liver injury on induction of adrenal necrosis by 7,12-dimethylbenz[a]anthracene (DMBA) were studied. Feeding rats a fatty diet or intraperitoneal administration of carbon tetrachloride induced hepatic injury. Whereas the susceptibility of the adrenal cortex to induction of necrosis and hemorrhage was greatly enhanced in rats fed a fatty diet, it was not influenced in those treated with CCI4. The mechanism by which the susceptibility of the adrenal cortex to injury by DMBA is increased is not clear. Induction of mammary cancer in rats with fatty liver was markedly retarded, but it was not affected in those treated with CCI4. Rats fed a fatty diet had transiently impaired endocrine functions, but these impairments were not present in CCI4-treated animals.
Precision public health must be at the centre of modern healthcare
Authors: David Prior
Journal: BMJ (2022)

The health of the population-what we now call public health-has been at the centre of great religions and civilisations for thousands of years.As we reflect on the lessons of covid-19, genomics, and artificial intelligence, digital technology may help us to put health security and prevention of illness at the centre of the health system.This is an extraordinary opportunity, but it requires a fundamental reassessment of how we deliver healthcare.
2016 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure
Authors: Piotr Ponikowski, Adriaan A. Voors, Stefan D. Anker, Héctor Bueno, John G. F. Cleland, Andrew J. S. Coats, Volkmar Falk, José Ramón González‐Juanatey, Veli‐Pekka Harjola, Ewa A. Jankowska, Mariell Jessup, Cecilia Linde, Petros Nihoyannopoulos, John T. Parissis, Burkert Pieske, Jillian P. Riley, Giuseppe M. C. Rosano, Luis M. Ruilope, Frank Ruschitzka, Frans H. Rutten, Peter van der Meer
Journal: European Journal of Heart Failure (2016)
Vasodilator Therapy for Heart Failure
Authors: Stanley A. Rubin
Journal: JAMA (1981)

Vasodilators are widely used in the treatment of heart failure patients even though the drugs are incompletely understood. Vasodilators oppose the excessive vasoconstriction of heart failure, but factors that control excessive vasomotor tone are poorly understood. Possible physiological benefits include more favorable distribution of blood flow and blood volume, but exact effects on blood vessels have been incompletely explored. As a result of vasodilation, preload and afterload reduction can improve cardiac performance, but the role of the blood vessels in the performance of the failing heart is not well understood. Clinical benefits include relief of dyspnea, improvement in tissue metabolism, and increase in exercise tolerance (in patients who have chronic heart failure). However, the degree of effectiveness among various causes of heart failure, different degrees of cardiovascular compensation, and different durations of failure is unknown. (<i>JAMA</i>1981;245:761-763)
Galunisertib plus neoadjuvant chemoradiotherapy in patients with locally advanced rectal cancer: a single-arm, phase 2 trial
Authors: Tomoko Yamazaki, Andrew J Gunderson, Miranda Gilchrist, Mark Whiteford, Maria X Kiely, Amanda Hayman, David O'Brien, Rehan Ahmad, Jeffrey V Manchio, Nathaniel Fox, Kayla McCarty, Michaela Phillips, Evelyn Brosnan, Gina Vaccaro, Rui Li, Miklos Simon, Eric Bernstein, Mary McCormick, Lena Yamasaki, Yaping Wu, Ashley Drokin, Trevor Carnahan, Yy To, William L Redmond, Brian Lee, Jeannie Louie, Eric Hansen, Matthew C Solhjem, Julie Cramer, Walter J Urba, Michael J Gough, Marka R Crittenden, Kristina H Young
Journal: The Lancet Oncology (2022)
Durvalumab plus tremelimumab in advanced or metastatic soft tissue and bone sarcomas: a single-centre phase 2 trial
Authors: Neeta Somaiah, Anthony P Conley, Edwin Roger Parra, Heather Lin, Behrang Amini, Luisa Solis Soto, Ruth Salazar, Carmelia Barreto, Honglei Chen, Swati Gite, Cara Haymaker, Elise F Nassif, Chantale Bernatchez, Akash Mitra, John Andrew Livingston, Vinod Ravi, Dejka M Araujo, Robert Benjamin, Shreyaskumar Patel, Maria A Zarzour, Sharjeel Sabir, Alexander J Lazar, Wei-Lien Wang, Najat C Daw, Xiao Zhou, Christina L Roland, Zachary A Cooper, Jaime Rodriguez-Canales, Andrew Futreal, Jean-Charles Soria, Ignacio I Wistuba, Patrick Hwu
Journal: The Lancet Oncology (2022)
De-escalation of radiotherapy after primary chemotherapy in cT1–2N1 breast cancer (RAPCHEM; BOOG 2010–03): 5-year follow-up results of a Dutch, prospective, registry study
Authors: Sabine R de Wild, Linda de Munck, Janine M Simons, Janneke Verloop, Thijs van Dalen, Paula H M Elkhuizen, Ruud M A Houben, A Elise van Leeuwen, Sabine C Linn, Ruud M Pijnappel, Philip M P Poortmans, Luc J A Strobbe, Jelle Wesseling, Adri C Voogd, Liesbeth J Boersma
Journal: The Lancet Oncology (2022)
An engineered dual function peptide to repair fractured bones
Authors: Stewart A. Low, Jeffery J. Nielsen, Cheyanne M. Coakley, Mini Thomas, Ephraim U. Mbachu, Christopher L. Chen, Yava Jones-Hall, Madeleine I. Tremblay, Jonathan R. Hicks, Philip S. Low
Journal: Journal of Controlled Release (2022)

Targeted drug delivery, often referred to as "smart" drug delivery, is a process whereby a therapeutic drug is delivered to specific parts of the body in a manner that increases its concentration at the desired sites relative to others. This approach is poised to revolutionize medicine as exemplified by the recent FDA approval of Cytalux (FDA approves pioneering drug for ovarian cancer surgery - Purdue University News) which is a folate-receptor targeted intraoperative near infrared (NIR) imaging agent that was developed in our laboratories. Fracture-associated morbidities and mortality affect a significant portion of world population. United states, Canada and Europe alone spent $48 billion in treating osteoporosis related fractures although this number doesn't count the economic burden due to loss in productivity. It is estimated that by 2050 ca 21 million hip fractures would occur globally which will be leading cause of premature death and disability. Despite the need for improvement in the treatment for fracture repair, methods for treating fractures have changed little in recent decades. Systemic delivery of fracture-homing bone anabolics holds great promise as a therapeutic strategy in this regard. Here we report the design of a fracture-targeted peptide comprised of a payload that binds and activates the parathyroid hormone receptor (PTHR1) and is linked to a targeting ligand comprised of 20 D-glutamic acids (D-Glu20) that directs accumulation of the payload specifically at fracture sites. This targeted delivery results in reduction of fracture healing times to <1/2 while creating repaired bones that are >2-fold stronger than saline-treated controls in mice. Moreover, this hydroxyapatite-targeted peptide can be administered without detectable toxicity to healthy tissues or modification of healthy bones in dogs. Additionally, since similar results are obtained upon treatment of osteoporotic and diabetic fractures in mice, and pain resolution is simultaneously accelerated by this approach, we conclude that this fracture-targeted anabolic peptide displays significant potential to revolutionize the treatment of bone fractures.
Long-acting formulation strategies for protein and peptide delivery in the treatment of PSED
Authors: Atul Garkal, Priyanka Bangar, Amarjitsing Rajput, Prashant Pingale, Namdev Dhas, Anam Sami, Khushboo Mathur, Shubham Joshi, Sonika Dhuri, Dhaivat Parikh, Srinivas Mutalik, Tejal Mehta
Journal: Journal of Controlled Release (2022)
Analysis of HIV-1 molecular transmission network reveals the prevalence characteristics of three main HIV-1 subtypes in Shenzhen, China
Authors: Dong Zhang, Hanping Li, Chenli Zheng, Jingwan Han, Hao Li, Yongjian Liu, Xiaolin Wang, Lei Jia, Siqi Li, Tianyi Li, Bohan Zhang, Lin Chen, Zhengrong Yang, Yongxia Gan, Yifan Zhong, Jingyun Li, Jin Zhao, Lin Li
Journal: Journal of Infection (2022)
Impact of SARS-CoV-2 Omicron variants on serum neutralization in a cohort of healthcare workers vaccinated with BNT162b2
Authors: Anna Gidari, Elisabetta Schiaroli, Samuele Sabbatini, Sabrina Bastianelli, Sara Pierucci, Chiara Busti, Daniela Francisci
Journal: Journal of Infection (2022)
CaMKII as a Therapeutic Target in Cardiovascular Disease
Authors: Oscar E. Reyes Gaido, Lubika J. Nkashama, Kate L. Schole, Qinchuan Wang, Priya Umapathi, Olurotimi O. Mesubi, Klitos Konstantinidis, Elizabeth D. Luczak, Mark E. Anderson
Journal: The Annual Review of Pharmacology and Toxicology (2022)

CaMKII (the multifunctional Ca
Cystic Fibrosis Modulator Therapies
Authors: Shijing Jia, Jennifer L. Taylor-Cousar
Journal: Annual Review of Medicine (2022)

Cystic fibrosis (CF) is an inherited multisystemic disease that can cause progressive bronchiectasis, pancreatic endocrine and exocrine insufficiency, distal intestinal obstruction syndrome, liver dysfunction, and other disorders. Traditional therapies focused on the treatment or prevention of damage to each organ system with incremental modalities such as nebulized medications for the lungs, insulin for diabetes, and supplementation with pancreatic enzymes. However, the advent of highly effective modulator therapies that target specific cystic fibrosis transmembrane conductance regulator protein malformations resulting from individual genetic mutations has transformed the lives and prognosis for persons with CF.
New Decongestion Strategies in an Evolving Heart Failure Landscape
Authors: G. Michael Felker
Journal: New England Journal of Medicine (2022)

Hospitalization for heart failure, usually due to volume overload, is among the most common reasons for hospitalization worldwide, and decongestion with loop diuretics is the primary focus of treatment in most patients.1 Despite the ubiquity of this clinical scenario in daily practice, high-quality data from randomized trials evaluating effective treatment approaches are sparse.2 The Diuretic Optimization Strategies Evaluation (DOSE) trial, published more than 11 years ago, compared strategies regarding dose level (high- vs. low-intensity loop diuretics) and means of administration (bolus vs. continuous infusion) in patients hospitalized with heart failure and congestion.3 Despite its modest size, that trial represented an . . .
Five-Year Outcomes of the Danish Cardiovascular Screening (DANCAVAS) Trial
Authors: Jes S. Lindholt, Rikke Søgaard, Lars M. Rasmussen, Anne Mejldal, Jess Lambrechtsen, Flemming H. Steffensen, Lars Frost, Kenneth Egstrup, Grazina Urbonaviciene, Martin Busk, Axel Cosmus Pyndt Diederichsen
Journal: New England Journal of Medicine (2022)

Limited data suggest a benefit of population-based screening for cardiovascular disease with respect to the risk of death.We performed a population-based, parallel-group, randomized, controlled trial involving men 65 to 74 years of age living in 15 Danish municipalities. The participants were randomly assigned in a 1:2 ratio to undergo screening (the invited group) or not to undergo screening (the control group) for subclinical cardiovascular disease. Randomization was based on computer-generated random numbers and stratified according to municipality. Only the control group was unaware of the trial-group assignments. Screening included noncontrast electrocardiography-gated computed tomography to determine the coronary-artery calcium score and to detect aneurysms and atrial fibrillation, ankle-brachial blood-pressure measurements to detect peripheral artery disease and hypertension, and a blood sample to detect diabetes mellitus and hypercholesterolemia. The primary outcome was death from any cause.A total of 46,611 participants underwent randomization. After exclusion of 85 men who had died or emigrated before being invited to undergo screening, there were 16,736 men in the invited group and 29,790 men in the control group; 10,471 of the men in the invited group underwent screening (62.6%). In intention-to-treat analyses, after a median follow-up of 5.6 years, 2106 men (12.6%) in the invited group and 3915 men (13.1%) in the control group had died (hazard ratio, 0.95; 95% confidence interval [CI], 0.90 to 1.00; P = 0.06). The hazard ratio for stroke in the invited group, as compared with the control group, was 0.93 (95% CI, 0.86 to 0.99); for myocardial infarction, 0.91 (95% CI, 0.81 to 1.03); for aortic dissection, 0.95 (95% CI, 0.61 to 1.49); and for aortic rupture, 0.81 (95% CI, 0.49 to 1.35). There were no significant between-group differences in safety outcomes.After more than 5 years, the invitation to undergo comprehensive cardiovascular screening did not significantly reduce the incidence of death from any cause among men 65 to 74 years of age. (Funded by the Southern Region of Denmark and others; DANCAVAS ISRCTN Registry number, ISRCTN12157806.).
Acetazolamide in Acute Decompensated Heart Failure with Volume Overload
Authors: Wilfried Mullens, Jeroen Dauw, Pieter Martens, Frederik H. Verbrugge, Petra Nijst, Evelyne Meekers, Katrien Tartaglia, Fabien Chenot, Samer Moubayed, Riet Dierckx, Philippe Blouard, Pierre Troisfontaines, David Derthoo, Walter Smolders, Liesbeth Bruckers, Walter Droogne, Jozine M. Ter Maaten, Kevin Damman, Johan Lassus, Alexandre Mebazaa, Gerasimos Filippatos, Frank Ruschitzka, Matthias Dupont
Journal: New England Journal of Medicine (2022)

Whether acetazolamide, a carbonic anhydrase inhibitor that reduces proximal tubular sodium reabsorption, can improve the efficiency of loop diuretics, potentially leading to more and faster decongestion in patients with acute decompensated heart failure with volume overload, is unclear.
BNP-Guided vs Symptom-Guided Heart Failure Therapy
Authors: Matthias Pfisterer, Peter Buser, Hans Rickli, Marc Gutmann, Paul Erne, Peter Rickenbacher, André Vuillomenet, Urs Jeker, Paul Dubach, Hansjürg Beer, Se-Il Yoon, Thomas Suter, Hans H. Osterhues, Michael M. Schieber, Patrick Hilti, Ruth Schindler, Hans-Peter Brunner-La Rocca, for the TIME-CHF Investigators
Journal: JAMA (2009)

2][3][4] However, these studies were small (n = 69, 1 n = 220, 2 n=130 3 ), not conclusive, 3,4 had limited follow-up, focused on younger patients, 2,3 and/or have not yet been published in detail. 3,4The concept of an intensified N-terminal BNP-guided therapy might be particularly attractive in older patients who are less physically active and in whom symptoms are less reliable, but they also may be more susceptible to drug-related adverse effects.Problems of heart failure increase with age. 5 Heart failure is the most common reason for hospitalization in patients aged 65 years or older. 6Older patients are underrepresented in randomized controlled trials, 7 mainly be-
Herniations of the Lumbar Intervertebral Disk in Children and Adolescents
Authors: David S. Bradford
Journal: JAMA (1969)

In 30 cases of surgically documented protrusions of the lumber intervertebral disk in children and adolescents, 14 patients displayed to a greater or lesser degree diagnostic difficulties and 16 patients underwent spinal fusion with laminectomy. Thorough study should be undertaken in all children and adolescents with back pain or sciatica, or both, and a ruptured lumbar intervertebral disk should be a prime consideration. Diagnostic problems are frequently due to the failure of the physician to appreciate this possibility. It is suggested that some cases of "disk space infection" may be herniations of the lumbar intervertebral disk.
Mechanical Occlusion of the Vertebral Artery
Authors: Elias A. Husni
Journal: JAMA (1966)

Acute insufficiency of the basilar artery, in the absence of organic disease, has been encountered in 20 patients. Attacks are transient and are precipitated by turning the head laterally and upwards. Two conditions are extant: (1) obliteration of vertebral artery flow by the contraction of the longus colli muscle and the scalene muscle at the level of the vertebral foramen of the sixth cervical vertebra and (2) a hypoplastic contralateral artery which does not adequately supply the basilar circulation. Vertebral angiography confirms the diagnosis by demonstrating one hypoplastic artery and a large contralateral artery that occludes upon forced lateral rotation of the head. The treatment consists of clearing the sixth vertebral foramen of all tendonous attachments and interposing a fat pedicle amongst the severed tendons to obviate their reattachment.
TAS-108, a Novel Oral Steroidal Antiestrogenic Agent, Is a Pure Antagonist on Estrogen Receptor α and a Partial Agonist on Estrogen Receptor β with Low Uterotrophic Effect
Authors: Yasuji Yamamoto, Jiro Shibata, Kazuhiko Yonekura, Kouji Sato, Akihiro Hashimoto, Yoshimi Aoyagi, Konstanty Wierzba, Shingo Yano, Tetsuji Asao, Aman U. Buzdar, Tadafumi Terada
Journal: Clinical Cancer Research (2005)

Abstract Purpose: Investigators are currently conducting phase II trials on TAS-108, a novel oral steroidal antiestrogenic agent. The purpose of this study is to investigate the molecular and pharmacologic properties of TAS-108 comparedwith other antiestrogenic agents such as tamoxifen,raloxifene, and fulvestrant. Experimental Design: The antagonistic or agonistic activities of these agents against both estrogen receptors (ER) α and β were compared in the reporter assay systems. Their effects on the uterus were evaluated in ovariectomized rat models. The antitumor activity of TAS-108 given p.o. was evaluated in both dimethylbenzanthracene-induced mammary tumor model and human breast cancer MCF-7 cell line xenografts. Results: TAS-108 inhibited the transactivation of ERα under the presence of 17β-estradiol (E2) and did not induce the transactivation of ERα in the absence of E2, unlike the agonistic activity of tamoxifen. On the other hand, it exhibited the most agonistic activity on ERβ among the antiestrogenic agents tested. When given p.o. in the ovariectomized rat, TAS-108 showed a much weaker estrogenic effect on utterine weight compared to tamoxifen, or with similar levels of raloxifene, a selective estrogen receptor modulator. Also, TAS-108 strongly inhibited tumor growth in dimethylbenzanthracene-induced mammary carcinomain the rat, the endogenous E2 model, at a dosage of 1 to 3 mg/kg/day. It also inhibited high exogenous E2, inducing tumor growth against MCF-7 xenografts at a dosage of 1 mg/kg/day without any toxic manifestation. Conclusions: Taken together, p.o. treatment with TAS-108 has a novel mode of action on ERs and inhibits E2-dependent tumor growth with little uterotrophic effect.
Serum Total Cholesterol and Mortality
Authors: Carlos Iribarren
Journal: JAMA (1995)

<h3>Objective.</h3> —To further investigate the relationship between serum total cholesterol (TC) level and mortality due to major causes. In particular, is the elevated mortality among persons with low TC levels due to confounding conditions that both lower TC level and increase the risk of mortality, and is the association between low or high TC level and mortality homogeneous in the population or, alternatively, restricted to persons with other risk factors? <h3>Study Design.</h3> —Prospective cohort study. <h3>Setting.</h3> —Free-living population in Oahu, Hawaii. <h3>Participants.</h3> —A total of 7049 middle-aged men of Japanese ancestry. <h3>Main Outcome Measures.</h3> —Age- and risk factor—adjusted mortality due to coronary heart disease, hemorrhagic stroke, cancer, chronic obstructive pulmonary disease, nonmalignant liver disease, trauma, miscellaneous and unknown, and all causes. <h3>Results.</h3> —During 23 years of follow-up, a total of 1954 deaths were documented (38% cancer, 25% cardiovascular, and 37% other). Men with low serum TC levels (&lt;4.66 mmol/L [&lt;180 mg/dL]) were found to have several adverse health characteristics, including a higher prevalence of current smoking, heavy drinking, and certain gastrointestinal conditions. In an age-adjusted model, and in relation to the reference group (4.66 to 6.19 mmol/L [180 to 239 mg/dL]), those in the lowest TC group (&lt;4.66 mmol/L [&lt;180 mg/dL]) were at significantly higher risk of mortality due to hemorrhagic stroke (relative risk [RR], 2.41; 95% confidence interval [CI], 1.45 to 4.00), cancer (RR, 1.41; 95% CI, 1.17 to 1.69), and all causes (RR, 1.23; 95% CI, 1.09 to 1.38). Adjustment for confounders in multivariate analysis (and exclusion of cases with prevalent disease at baseline and deaths through year 5) did not explain the risk of fatal hemorrhagic stroke but reduced the excess risk of cancer mortality by 51% (to 1.20 from 1.41) and reduced the excess risk of all-cause mortality by 56% (to 1.10 from 1.32) in the low TC group. In addition, there were clear differences in the patterns of risk when comparing men with and without selected risk factors (ie, smoking, alcohol consumption, and untreated hypertension). <h3>Conclusions.</h3> —We conclude that the excess mortality at low TC levels can be partially explained by confounding with other determinants of death and by preexisting disease at baseline, and TC-mortality associations are not homogeneous in the population. In our study, TC level was not associated with increased cancer or all-cause mortality in the absence of smoking, high alcohol consumption, and untreated hypertension. (<i>JAMA</i>. 1995;273:1926-1932)